ACID-BASE BALANCE REGULATION OF RENAL METABOLISM

肾脏代谢的酸碱平衡调节

• 批准号: 3225997
• 负责人: DAVID P SIMPSON
• 金额: $ 17.11万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-12-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3225997
• 关键词: acid base balance; acidosis; alkalosis; ammonia; anions; bicarbonates; citrates; glutamine; high performance liquid chromatography; homeostasis; ion transport; kidney metabolism; membrane permeability; membrane potentials; mitochondrial membrane; oxoglutarate dehydrogenase; phosphates; radiotracer; renal tubular transport; renal tubule; respiratory acidosis; tissue /cell culture; ultracentrifugation

This project is an investigation into regulation of intermediary metabolism in the kidney by acid-base changes and the relationship to physicologic processes involved in acid-base homeostasis. The emphasis in the project is to relate properties of the inner mitochondrial membrane to two different metabolic responses by the kidney to alterations in acid-base balance. (1) During chronic metabolic acidosis renal ammoniagenesis from glutamine increases strikingly. Previous work has suggested that a major factor in this adaptive response is an increase in acidosis in glutamine transport by its carrier in the inner mitochondrial membrane, leading to delivery of more glutamine to phosphate dependent glutaminase. Further evidence for adaptation of the glutamine transporter will be sought in studies on mitochondria from dogs with chronic metabolic or respiratory acidosis. Changes in mitochondrial glutamine transport and metabolism will be correlated with NH4+excretion, NH3 synthesis and glutamine utilization in intact animals with chronic metabolic or respiratory acidosis. (2) Levels in renal cortex of a number of citric acid cycle and related substrates decrease in acute metabolic acidosis and increase in metabolic alkalosis. We postulate that these changes are the result of substrate shifts occurring in response to variations in the mitochondrial pH gradient. Studies will be carried out in isolated kidney tubules and in mitochondria to determine the validity of this hypothesis.

本课题是对中间体代谢调控的研究。 肾脏酸碱变化及其与生理的关系 涉及酸碱平衡的过程。项目中的重点 是将线粒体内膜的特性与两种 肾脏对酸碱变化的不同代谢反应 平衡。(1)慢性代谢性酸中毒期间肾脏氨化 谷氨酰胺显著增加。先前的研究表明，一个主要的 这种适应性反应的因素是谷氨酰胺酸中毒的增加。 通过其载体在线粒体膜内的运输，导致 将更多的谷氨酰胺传递给磷酸依赖的谷氨酰胺酶。进一步 将在#年寻找谷氨酰胺转运体适应的证据 慢性代谢和呼吸系统疾病犬线粒体的研究 酸中毒。线粒体谷氨酰胺转运和代谢的变化将 与NH4+排泄、NH3合成和谷氨酰胺利用相关 在患有慢性代谢性或呼吸性酸中毒的完整动物身上。(2) 肾皮质中若干柠檬酸循环的水平及其相关 急性代谢性酸中毒底物减少代谢性增加 碱中毒。我们假设这些变化是底物的结果。 线粒体pH变化时发生的变化 渐变。研究将在分离的肾小管和 以确定这一假说的真实性。